A Prospective Randomised, Double-blinded Cross-over Study to Investigate the Effects of Racemic and S-ketamine on Cerebral Blood Flow on Healthy Volunteers With MRI-ASL

In this investigator-initiated randomised, double-blinded, crossover study, adult healthy volunteers will be randomised to receive, as 60-second iv bolus injections on two different occasions with at least seven days interval, 0.3 mg kg of S-ketamine (Ketanest® 5.0 mg/ ml, Pfizer, USA) or 0.6 mg/kg of racemic ketamine (Ketalar® 10 mg/ml, Pfizer, USA) supplied by the hospital pharmacy.

The volunteers will consecutively be given specific inclusion numbers and randomized according to a schedule with corresponding randomization codes prepared in advance by the Research & Development Centre of the Skåne Region, Skåne University Hospital, Lund, Sweden. Before each investigation, a sealed envelope marked with the corresponding inclusion number, will be opened in a separate room by a nurse not taking further part in the study. The nurse prepared the study drug according to the randomization code in a 20 ml syringe based on a bodyweight-based dosing schedule, and diluted the study drug with saline to a total volume of 20 ml. The prepared syringe, marked with the inclusion number, date and signature, will be handed over to the investigator.

After an initial 10-minute period of dynamic baseline measurements, the study drug will be injected manually by the investigator. ASL measurements will be made over a 45-minute study period starting from the injection of study drug, and the volunteer will be brought to the preparation room for at least 60 minutes of further supervision until clinical routine criteria for postoperative discharge will be met.

Fourteen healthy (American Society of Anaesthesiologists physical status 1) adult volunteers will be included after physical examinations and individual written informed consents. Female subjects will be required to use effective anti-conception methods during the study period. The volunteers will have to refrain from caffeine, nicotine, alcohol and medications for 72 hours, and fast for six hours, but will be allowed to drink water until two hours before each ASL-MRI investigation.

Each volunteer will be offered ear plugs, asked to rest with eyes closed during the scanning procedure, and left undisturbed throughout the study period. Oxygen 2 l/min will be delivered by nasal cannula.